Approximately 34 million adult Americans, and 20% of this country's children are obese Increased rates of hypertension, stroke, diabetes, and disordered blood lipids have been clearly related to obesity. The annual cost of ineffective treatment for obesity, and for its medical complications, is in the tens of billions of dollars annually in the U.S. alone. In the most fundamental physico-chemical terms, obesity is the result of a period during which energy input (food intake) exceeds energy output (mainly resting energy expenditure and physical activity). Three hypotheses are being examined: I. Changes in the number of stored calories (adipose tissue) above or below that which is 'normative' for a given individual are accompanied by changes in energy metabolism which tend to return stored calories to their initial level. II. Obese and non-obese individuals have similar responses to experimental changes in caloric storage, thus "defending" adipose tissue depots of different size by the same metabolic mechanisms. III. Candidate systems for effecting these changes in energy metabolism can be identified, and include the autonomic nervous system, skeletal muscle physiology, thyroid metabolism, adipose tissue physiology, and glucose/insulin homeostasis. In 10 obese, 20 non- obese, and 15 long-term formerly obese subjects, measurements will be made of components of: 1.) energy metabolism (hood and chamber calorimetry, caloric requirement to maintain body weight, differential excretion of isotopes of heavy water, thermic effect of feeding, energy cost of physical activity, autonomic nervous activity, glucose/insulin, thyroid, and catecholamine homeostasis); 2.) body composition, (hydrodensitometry, water space y isotope dilution, dual photon beam absorptiometry); and 3.) adipose tissue biochemistry (acylglyceride synthesis, basal lipolysis, fatty acid re-esterification, and adrenoreceptor status). These measures will be repeated under circumstances of long term weight stability at weight plateaus equal to, above, and below initial weight. Results from the 45 subjects to be studied in this grant cycle - combined with those from the subjects upon whom studies have been completed or are currently underway - will permit us to quantify the contribution of alterations in energy efficiency (up or down) to the occurrence and/or maintenance of obesity, and to specify the relative importance of specific components of energy metabolisms to these processes.